Antigens and T cell epitopes from cockroach and methods of making and using same

Inventors

Peters, Bjoern • Sette, Alessandro

Assignees

La Jolla Institute for Allergy and Immunology

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Publication Number

US-11505581-B2

Patent

Publication Date

2022-11-22

Expiration Date


Abstract

The specificity of CD4+ TH responses of German cockroach (Bla g) antigens, and whether differences exist in magnitude or functionality as a function of disease severity, is disclosed. Also disclosed are novel German cockroach allergens and epitopes.

Core Innovation

The invention relates to a pharmaceutical composition that comprises a peptide and an adjuvant. The peptide comprises an amino acid sequence selected from specified cockroach T-cell epitopes, including TIPYYTKKFDEVVKA (SEQ ID NO:1), HDDRLGFLTFCPTNL (SEQ ID NO:7), KNRTTIRGRTKFEGN (SEQ ID NO:8), DRKMYWQFKMDKIQI (SEQ ID NO:9), IRGRTKFEGNKFTID (SEQ ID NO:11), and additional peptides defined by SEQ ID NOs 12, 14-18, 20-23.

The invention relates to the discovery and characterization of CD4+ T-cell responses to German cockroach (Blattella germanica) allergens, including determination of T helper subset balance across Th1, Th2, Th17, Treg/TR1, and Tfh. It links the magnitude and functionality of anti-cockroach/allergen responses with clinical asthma severity, and includes allergen/epitope reactivity and immunodominance differences across subject groups.

The composition and cockroach epitopes are used to induce immunological tolerance and suppress allergic responses, including immunotherapy/specific immunotherapy (SIT). The disclosure also describes diagnostic and detection approaches that support immune modulation assessment, including contacting subject cells with peptide sets and determining immune modulation using cell-contact assays, including T-cell assays and ELISPOT.

Claims Coverage

The claim set contains four main inventive features anchored around composition, immune modulation, tolerance induction, and subject-cell-based peptide identification for cockroach allergy treatment.

Peptide composition with selected cockroach T-cell epitopes and an adjuvant

A pharmaceutical composition comprising a peptide consisting of an amino acid sequence selected from TIPYYTKKFDEVVKA (SEQ ID NO:1), HDDRLGFLTFCPTNL (SEQ ID NO:7), KNRTTIRGRTKFEGN (SEQ ID NO:8), DRKMYWQFKMDKIQI (SEQ ID NO:9), IRGRTKFEGNKFTID (SEQ ID NO:11), NDIEKRVPFSHDDRL (SEQ ID NO:12), VLEKLEAGFAKLAAS (SEQ ID NO:14), NYAIVEGCPAAANGH (SEQ ID NO:15), GIRIYVDVVLNQMSG (SEQ ID NO:16), RWRQIFNMVGFRNAV (SEQ ID NO:17), NIACLLHNKYDSTKS (SEQ ID NO:18), LNIFTNNLGRINTHV (SEQ ID NO:20), KTPVLEIDGKQTHQS (SEQ ID NO:21), PAYFKMNSPSLWKYN (SEQ ID NO:22), and PKSMLLNIFTNNLGR (SEQ ID NO:23), and an adjuvant.

Immune response modulation to a Cockroach allergen by administering the composition

A method of modulating an immune response to a Cockroach allergen in a subject by administering an amount of the pharmaceutical composition sufficient to achieve the modulation.

Inducing immunological tolerance to a Cockroach allergen

A method including inducing immunological tolerance in a subject to the Cockroach allergen.

Treating cockroach allergy with peptide identified by subject-cell immune modulation

A method of treating cockroach allergy in a subject by administering an effective amount of a peptide identified by contacting a subject cell with the peptide and determining whether the peptide modulates immune activity of the contacted cell.

The claims cover a composition that combines specific defined cockroach-derived peptide epitopes with an adjuvant, with dependent claims refining use toward immune modulation against cockroach allergens, including inducing immunological tolerance and treating cockroach allergy in a subject.

Stated Advantages

Induces immunological tolerance and suppresses allergic responses.

Modulates immune responses against cockroach allergens.

Induces immunological tolerance related to cockroach allergen immune responses.

Treats cockroach allergy in a subject.

Documented Applications

Treating cockroach allergy in a subject, including a human subject.

Modulating immune responses to a Cockroach allergen in a subject.

Diagnostic or immune assessment use via contacting subject cells with peptide sets and determining immune modulation, with application to allergic responses including asthma and allergic rhinitis.

Immunotherapy/specific immunotherapy (SIT) to induce immunological tolerance to cockroach allergens.

Therapeutic treatment of cockroach allergy in a subject, including a human subject.

Use in the context of modulating CD4+ T-cell responses to German cockroach allergens relevant to clinical asthma severity.

Diagnostic sets mapping epitope sequences to allergens/proteins, including sets associated with Asthma vs CNT.

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